Oxaliplatin and Capecitabine With or Without an Hepatic Arterial Infusion With Floxuridine in Treating Patients Who Are Undergoing Surgery and/or Ablation for Liver Metastases Due to Colorectal Cancer

NCT ID: NCT00268463

Last Updated: 2013-05-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2008-06-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, capecitabine, and floxuridine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hepatic arterial infusion uses a catheter to carry tumor-killing substances, such as chemotherapy, directly into the liver. Giving chemotherapy in different ways may kill more tumor cells. It is not yet known whether giving oxaliplatin and capecitabine together with an hepatic arterial infusion with floxuridine is more effective than giving oxaliplatin and capecitabine alone in treating patients who are undergoing surgery and/or ablation for liver metastases due to colorectal cancer.

PURPOSE: This randomized phase III trial is studying oxaliplatin, capecitabine, and an hepatic arterial infusion with floxuridine to see how well they work compared to oxaliplatin and capecitabine in treating patients who are undergoing surgery and/or ablation for liver metastases due to colorectal cancer.

Detailed Description

OBJECTIVES:

Primary

• Compare progression-free interval (PFI) in patients undergoing surgical resection and/or ablation for hepatic metastases from colorectal cancer treated with adjuvant therapy comprising oxaliplatin and capecitabine with vs without hepatic arterial infusion of floxuridine.

Secondary

• Compare overall survival and liver PFI between the two treatment groups.
• Assess toxicity in each of the treatment regimens.
• Compare self-reported symptoms between two treatment groups.
• Compare quality of life in each of the treatment regimens.

Tertiary

• Examine the prognostic worth, in terms of PFI, of specific molecular markers in hepatic metastases.

OUTLINE: This is a randomized study. Patients are stratified according to intended surgical technique (surgical resection alone vs cryoablation or radiofrequency ablation [RFA] alone vs combination of resection and ablation) and prior adjuvant chemotherapy regimen (chemotherapy with vs without oxaliplatin vs no chemotherapy). Patients are randomized to 1 of 2 treatment arms.

All patients undergo surgical resection and/or hepatic cryoablation or RFA to remove a maximum of 6 colorectal hepatic metastases. Patients randomized to arm II also undergo intra-arterial catheter and if applicable, pump placement.

• Arm 1 (oxaliplatin and capecitabine): Within 4-6 weeks after surgery and/or ablation, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
• Arm 2 (oxaliplatin, capecitabine, and hepatic arterial infusion of floxuridine): Within 4-6 weeks after surgery and/or ablation, patients receive a continuous hepatic arterial infusion of floxuridine on days 1-14, oxaliplatin IV over 2 hours on day 22, and oral capecitabine twice daily on days 22-35. Treatment repeats every 42 days for 4 courses in the absence of unacceptable toxicity. Beginning with course 5, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment with oxaliplatin and capecitabine repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 4-6 weeks after surgery or ablation, approximately 18 weeks after beginning of chemotherapy, and 4-6 weeks after beginning the last cycle of chemotherapy.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

Conditions

Colorectal Cancer; Metastatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: Capecitabine + Oxaliplatin

Within 4-6 weeks after surgery and/or ablation, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity.

Group Type: ACTIVE_COMPARATOR

capecitabine

Intervention Type: DRUG

Oral capecitabine 850 mg/m2 twice daily on days 1-14 every 21 days for 8 cycles: Arm 1

Oral capecitabine 850 mg/m2 twice daily on days 22-35 every 42 days for 4 cycles and then on days 1-14 every 21 days for 4 cycles: Arm 2

oxaliplatin

Intervention Type: DRUG

Oxaliplatin 130 mg/m2 IV over 2 hours on day 1 every 21 days for 8 cycles: Arm 1

Oxaliplatin 130 mg/m2 IV over 2 hours on day 22 every 42 days for 4 cycles and then on day 1 every 21 days for 4 cycles: Arm 2

Arm 2: Floxuridine + Oxaliplatin + Capecitabine

Within 4-6 weeks after surgery and/or ablation, patients receive a continuous hepatic arterial infusion of floxuridine on days 1-14, oxaliplatin IV over 2 hours on day 22, and oral capecitabine twice daily on days 22-35. Treatment repeats every 42 days for 4 cycles in the absence of unacceptable toxicity. Beginning with cycle 5, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment with oxaliplatin and capecitabine repeats every 21 days for 4 cycles.

Group Type: EXPERIMENTAL

capecitabine

Intervention Type: DRUG

Oral capecitabine 850 mg/m2 twice daily on days 1-14 every 21 days for 8 cycles: Arm 1

Oral capecitabine 850 mg/m2 twice daily on days 22-35 every 42 days for 4 cycles and then on days 1-14 every 21 days for 4 cycles: Arm 2

floxuridine

Intervention Type: DRUG

Continuous hepatic arterial infusion of floxuridine 0.2 mg/kg on days 1-14 every 42 days for 4 cycles

oxaliplatin

Intervention Type: DRUG

Oxaliplatin 130 mg/m2 IV over 2 hours on day 1 every 21 days for 8 cycles: Arm 1

Oxaliplatin 130 mg/m2 IV over 2 hours on day 22 every 42 days for 4 cycles and then on day 1 every 21 days for 4 cycles: Arm 2

Interventions

capecitabine

Oral capecitabine 850 mg/m2 twice daily on days 1-14 every 21 days for 8 cycles: Arm 1

Oral capecitabine 850 mg/m2 twice daily on days 22-35 every 42 days for 4 cycles and then on days 1-14 every 21 days for 4 cycles: Arm 2

Intervention Type: DRUG

floxuridine

Continuous hepatic arterial infusion of floxuridine 0.2 mg/kg on days 1-14 every 42 days for 4 cycles

Intervention Type: DRUG

oxaliplatin

Oxaliplatin 130 mg/m2 IV over 2 hours on day 1 every 21 days for 8 cycles: Arm 1

Oxaliplatin 130 mg/m2 IV over 2 hours on day 22 every 42 days for 4 cycles and then on day 1 every 21 days for 4 cycles: Arm 2

Intervention Type: DRUG

Other Intervention Names

Xeloda; FUDR; Eloxatin

Eligibility Criteria

Inclusion Criteria

• Synchronous or metachronous metastatic disease confined to the liver

• No more than 6 hepatic metastatic lesions that can potentially be resected or ablated
• For patients presenting with synchronous lesion(s) in the colon and/or rectum, the primary tumors must, in the opinion of the investigator, appear to be completely resectable
• Must be able to undergo surgery and/or ablation within 28 days following randomization
• No evidence of extrahepatic metastases
• No prior colorectal metastases
• No recurrent colorectal cancer concurrent with hepatic metastases

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 5 years, excluding their colorectal cancer
• Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1
• No other malignancy within the past 5 years except carcinoma in situ of the cervix, melanoma in situ, basal cell or squamous cell skin cancer, or carcinoma of the colon or rectum
• Absolute granulocyte count ≥ 1,200/mm^3
• Platelet count ≥ 100,000/mm^3
• PT/international normalized ratio (INR) ≤ 1.5 unless patient is on therapeutic doses of anticoagulant medication
• Total bilirubin ≤ upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 ULN
• aspartate aminotransferase (AST) ≤ 2.5 times ULN
• Calculated creatinine clearance > 50 mL/min
• Not pregnant or lactating
• Negative pregnancy test
• Patients with child bearing potential must agree to use adequate contraception
• Able to swallow oral medication
• No preexisting chronic hepatic disease (e.g., chronic active hepatitis or cirrhosis)
• No grade 3 or 4 anorexia or nausea
• No vomiting ≥ grade 2
• No clinically significant peripheral neuropathy defined as ≥ grade 2 neurosensory or neuromotor toxicity
• No psychiatric or addictive disorders or other condition that, in the opinion of the investigator, would preclude study participation

PRIOR CONCURRENT THERAPY:

• Prior adjuvant fluorouracil alone or in combination with levamisole, leucovorin calcium, irinotecan hydrochloride, or oxaliplatin allowed if these regimens were completed > 6 months ago
• No prior resection/ablation, hepatic arterial infusion therapy, or any systemic chemotherapy for metastatic disease

• Prior excisional biopsy allowed
• No prior radiotherapy to the liver
• No concurrent bevacizumab in patients who have had pump/catheter placement receiving hepatic arterial infusion of floxuridine

• Patients who meet specific situations outlined in the protocol and who have not had pump placement may receive bevacizumab at the physician's discretion
• No concurrent halogenated antiviral agents such as sorivudine or brivudine in patients receiving fluorouracil, floxuridine, or capecitabine
• No concurrent filgrastim (G-CSF), pegfilgrastim, or sargramostim (GM-CSF) as primary prophylaxis for neutropenia

• Following neutropenic events, these drugs may be used at the physician's discretion during subsequent cycles
• No other concurrent cancer therapy
• No other concurrent investigational agents

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NSABP Foundation Inc

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Norman Wolmark, MD

Role: PRINCIPAL_INVESTIGATOR

NSABP Foundation Inc

Locations

Cancer Care Center at John Muir Health - Concord Campus

Concord, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Veterans Affairs Medical Center - Loma Linda (Pettis)

Loma Linda, California, United States

Kaiser Permanente Medical Center - Walnut Creek

Walnut Creek, California, United States

John Muir/Mt. Diablo Comprehensive Cancer Center

Walnut Creek, California, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Washington Cancer Institute at Washington Hospital Center

Washington D.C., District of Columbia, United States

Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, United States

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, United States

Central Baptist Hospital

Lexington, Kentucky, United States

Louisville Oncology at Norton Cancer Center

Louisville, Kentucky, United States

CCOP - Ochsner

New Orleans, Louisiana, United States

Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center

Baltimore, Maryland, United States

Saint Joseph Mercy Cancer Center

Ann Arbor, Michigan, United States

Borgess Medical Center

Kalamazoo, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Altru Cancer Center at Altru Hospital

Grand Forks, North Dakota, United States

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, United States

Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center

Portland, Oregon, United States

CCOP - Columbia River Oncology Program

Portland, Oregon, United States

Providence St. Vincent Medical Center

Portland, Oregon, United States

St. Luke's Cancer Network at St. Luke's Hospital

Bethlehem, Pennsylvania, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

UMC Southwest Cancer and Research Center

Lubbock, Texas, United States

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, United States

Virginia Oncology Associates - Hampton

Hampton, Virginia, United States

Mary Babb Randolph Cancer Center at West Virginia University Hospitals

Morgantown, West Virginia, United States

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

U10CA012027

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NSABP C-09

Identifier Type: -

Identifier Source: org_study_id